Inclusion Criteria:

• Participants must have histologically proven primary (or locally recurrent after prior surgery) soft tissue sarcoma of the retroperitoneum. Patients in the Phase II portion of the trial will be primary soft tissue sarcomas only. Extraskeletal chondrosarcoma is allowed.  Pathology must be reviewed prior to study entry.

  • Note: For patients with retroperitoneal neoplasms that have ambiguous histological and/or immunohistochemical findings, the diagnoses of carcinoma, melanoma, and lymphoma should be excluded by immunohistochemical studies with antibodies to broad spectrum cytokeratin (AE1/AE3), S-100, CD45, or LCA (leucocyte common antigen), respectively. If these diagnoses are excluded by immunohistochemistry, then patients presenting with primary non-visceral retroperitoneal masses that are felt to be "consistent with sarcoma" shall be considered eligible for this trial.

• Participants must have histologically proven primary (or locally recurrent after prior surgery) soft tissue sarcoma of the retroperitoneum. Patients in the Phase II portion of the trial will be primary soft tissue sarcomas only. Extraskeletal chondrosarcoma is allowed.  Pathology must be reviewed at treating institution or DF/HCC affiliate  prior to study entry (for locally recurrent participants, biopsy and pathology review may be from time of original diagnosis). 
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral CT scan.
• No prior radiation therapy for retroperitoneal sarcoma is allowed.
• Age 18 years or older.  Children are excluded from this study but may be eligible for pediatric sarcoma trials of radiation therapy.
• Life expectancy of greater than 2 years.
• ECOG performance status <1.
• Participants must have normal organ and marrow function as defined below:
  • Leukocytes > 3,000/mcL;
  • Absolute neutrophil count > 1,500/mcL;
  • Platelets > 100,000/mcL;
  • Hemoglobin > 8.0g/dl;
    • Note: the use of transfusion or other intervention to achieve Hgb > 8.0 g/dl is acceptable.
  • Total bilirubin within normal institutional limits;
  • AST (SGOT)/ALT (SGPT) < 2.5 X institutional upper limit of normal;
  • For women of childbearing potential, negative urine or serum pregnancy test within 6 weeks prior to study entry.
• No distant metastases, based upon the following minimum diagnostic workup:
  • History and physical exam including a detailed description of the location, size and stage of the sarcoma, within 10 weeks prior to study entry;
  • CT or MRI with contrast of the abdomen and pelvis within 8 weeks prior to study entry; the maximal dimension of the primary tumor will be measured in CT and MRI images; and
  • CT scan of the chest within 8 weeks prior to study entry.
• The effects of radiation therapy on the developing human fetus have been known to be teratogenic.  Women of child-bearing potential and men must agree to use adequate contraception (i.e., hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• The ability to understand and the willingness to sign a written informed consent document.
• Participant must be evaluated by surgical oncologist and felt to have potentially resectable tumor and be medically fit for proposed surgery.

Exclusion Criteria:

Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study:

• Participants who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to study entry or those with adverse events due to agents administered more than 4 weeks earlier that have not  resolved to < Grade 1 per CTCAE v. 4.
• Participants may not be receiving any other investigational agents.
• Participants with sarcoma of head and neck, lung, heart or extremity origin; or histopathology demonstrating rhabdomyosarcoma, extraosseous primitive neuroectodermal tumor (PNET) soft tissue Ewing’s sarcoma, osteosarcoma, Kaposi’s sarcoma, angiosarcoma, aggressive fibromatosis (desmoid tumor), or dermatofibrosarcoma protuberans or chondrosarcoma other than extraskeletal chondrosarcoma; or well differentiated liposarcoma where the target volume cannot be adequately distinguished from the normal retroperitoneal fat are excluded.
• Participants with multifocal disease, lymph node or distant metastases.
  • Note: multiple pulmonary nodules <8 mm without a histological diagnosis detected incidentally in a non-screening CT scan may not be a basis for study exclusion because of the sensitivity/specificity of the CT scans of the chest/abdomen/pelvis.
• History of sensitivity to, or history of conditions that are known to cause sensitivity to, radiation therapy.
• Participants for whom intraoperative or post-operative radiation therapy is planned as part of the overall primary tumor treatment.
• Uncontrolled, intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because radiation is known to have teratogenic effects.
• Individuals with a history of a different invasive malignancy are eligible per the discretion of the treating investigator and review by the principal investigator.
• HIV-positive individuals on combination antiretroviral therapy are ineligible because of the potential for increased sensitivity to radiation therapy. (American Journal of Clinical Oncology: October 1998: 21(5), 479-81.